ES2315022T3 - Metodo para la produccion de fvii. - Google Patents

Metodo para la produccion de fvii. Download PDF

Info

Publication number: ES2315022T3
Authority: ES; Spain
Prior art keywords: baselineskip; kex2; fvii; endoprotease; cells
Prior art date: 1998-11-06
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES99955836T

Other languages

English (en)

Spanish (es)

Inventor

Helle Woldike

Finn C. Wiberg

Lars Soegaard Nielsen

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novo Nordisk Health Care AG

Original Assignee

Novo Nordisk Health Care AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1998-11-06

Filing date

1999-11-05

Publication date

2009-03-16

1999-11-05 Application filed by Novo Nordisk Health Care AG filed Critical Novo Nordisk Health Care AG

2009-03-16 Application granted granted Critical

2009-03-16 Publication of ES2315022T3 publication Critical patent/ES2315022T3/es

2019-11-05 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

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VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
230000003612 virological effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6437—Coagulation factor VIIa (3.4.21.21)
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21021—Coagulation factor VIIa (3.4.21.21)

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Organic Chemistry (AREA)
Wood Science & Technology (AREA)
Genetics & Genomics (AREA)
Bioinformatics & Cheminformatics (AREA)
Zoology (AREA)
Biomedical Technology (AREA)
General Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Biotechnology (AREA)
Microbiology (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Crystals, And After-Treatments Of Crystals (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

ES99955836T 1998-11-06 1999-11-05 Metodo para la produccion de fvii. Expired - Lifetime ES2315022T3 (es)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
DKPA199801436		1998-11-06
DK199801436		1998-11-06
DK199801439		1998-11-09
DKPA199801439		1998-11-09
US10806598P	1998-11-12	1998-11-12
PCT/DK1999/000607 WO2000028065A1 (fr)	1998-11-06	1999-11-05	Technique de production du facteur vii

Publications (1)

Publication Number	Publication Date
ES2315022T3 true ES2315022T3 (es)	2009-03-16

Family

ID=27221287

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES99955836T Expired - Lifetime ES2315022T3 (es)	1998-11-06	1999-11-05	Metodo para la produccion de fvii.

Country Status (8)

Country	Link
US (2)	US6329176B1 (fr)
EP (1)	EP1127154B1 (fr)
JP (1)	JP4463988B2 (fr)
AT (1)	ATE408020T1 (fr)
AU (1)	AU1262900A (fr)
DE (1)	DE69939548D1 (fr)
ES (1)	ES2315022T3 (fr)
WO (1)	WO2000028065A1 (fr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7247708B2 (en)	1997-10-23	2007-07-24	Regents Of The University Of Minnesota	Modified vitamin K-dependent polypeptides
US6747003B1 (en)	1997-10-23	2004-06-08	Regents Of The University Of Minnesota	Modified vitamin K-dependent polypeptides
SK782002A3 (en)	1999-07-21	2003-08-05	Lexigen Pharm Corp	FC fusion proteins for enhancing the immunogenicity of protein and peptide antigens
CA2739933A1 (fr)	2000-02-11	2001-08-16	Bayer Healthcare Llc	Molecules de type facteur vii ou viia
US7812132B2 (en)	2000-04-28	2010-10-12	Regents Of The University Of Minnesota	Modified vitamin K-dependent polypeptides
US7220837B1 (en)	2000-04-28	2007-05-22	Regents Of The University Of Minnesota	Modified vitamin K-dependent polypeptides
US20030211094A1 (en)	2001-06-26	2003-11-13	Nelsestuen Gary L.	High molecular weight derivatives of vitamin k-dependent polypeptides
BR0114373A (pt) *	2000-10-02	2004-02-17	Novo Nordisk As	Célula hospedeira eucariótica, métodos para a produção de fvii e de fviia ou de suas variantes, de uma proteìna dependente de vitamina k e de uma célula hospedeira eucariótica produtora de fvii ou de seu análogo, vetor recombinante, fvii e fviia recombinante ou suas variantes, e, proteìna dependente de vitamina k recombinante
EP1434857B1 (fr)	2001-10-02	2007-08-01	Novo Nordisk Health Care AG	Technique de production de proteines de recombinaison dans des cellules eucaryotes
WO2003093465A1 (fr)	2002-04-30	2003-11-13	Maxygen Holdings Ltd.	Variants polypeptidiques du facteur vii ou viia
CA2519873C (fr)	2003-03-20	2012-12-18	Maxygen Holdings Ltd.	Variants de fvii ou fviia
AU2004238263A1 (en) *	2003-05-06	2004-11-25	Syntonix Pharmaceuticals, Inc.	Inhibition of drug binding to serum albumin
US7348004B2 (en)	2003-05-06	2008-03-25	Syntonix Pharmaceuticals, Inc.	Immunoglobulin chimeric monomer-dimer hybrids
PL2298347T3 (pl)	2003-05-06	2016-03-31	Bioverativ Therapeutics Inc	Białka chimeryczne czynnika krzepnięcia do leczenia zaburzenia hemostazy
TWI353991B (en) *	2003-05-06	2011-12-11	Syntonix Pharmaceuticals Inc	Immunoglobulin chimeric monomer-dimer hybrids
RU2373282C2 (ru)	2003-06-19	2009-11-20	Байер Хелткэр Ллк	ВАРИАНТЫ ДОМЕНА GLA ФАКТОРА VII ИЛИ VIIa
ES2381110T3 (es)	2003-09-09	2012-05-23	Novo Nordisk Health Care Ag	Polipéptidos de factor VII de coagulación
US8461115B2 (en)	2006-03-16	2013-06-11	Stellaris Pharmaceuticals Aps	Methods for local treatment with factor VII
NO2440239T3 (fr)	2009-06-09	2018-02-10
US10172949B2 (en)	2009-06-09	2019-01-08	Prolong Pharmaceuticals, LLC	Hemoglobin compositions
US10172950B2 (en)	2009-06-09	2019-01-08	Prolong Pharmaceuticals, LLC	Hemoglobin compositions
RU2448160C1 (ru) *	2010-11-11	2012-04-20	Закрытое акционерное общество "ГЕНЕРИУМ"	РЕКОМБИНАНТНАЯ ПЛАЗМИДНАЯ ДНК pAP271, КОДИРУЮЩАЯ ПОЛИПЕПТИД ФАКТОРА VII СВЕРТЫВАЕМОСТИ КРОВИ ЧЕЛОВЕКА, И ЛИНИЯ КЛЕТОК Mesocricetus auratus ВНК 21 k.13 (2H7) - ПРОДУЦЕНТ РЕКОМБИНАНТНОГО ФАКТОРА VII СВЕРТЫВАЕМОСТИ КРОВИ ЧЕЛОВЕКА
WO2014144549A1 (fr)	2013-03-15	2014-09-18	Biogen Idec Ma Inc.	Préparations contenant un polypeptide du facteur ix
BR102015012334A2 (pt)	2015-05-27	2016-11-29	Fundação Hemoct De Ribeirão Preto Fundherp	processo de produção do fator vii de coagulação sanguínea e fator vii de coagulação sanguínea

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5516650A (en) *	1985-06-27	1996-05-14	Zymogenetics, Inc.	Production of activated protein C
CA1340740C (fr) *	1987-12-08	1999-09-14	Eileen R. Mulvihill	Coexpressiondans des cellules eucaryotes
ATE158816T1 (de) *	1990-11-26	1997-10-15	Genetics Inst	Expression von pace in wirtszellen und verfahren zu dessen verwendung
ATE157703T1 (de) *	1991-12-16	1997-09-15	Ciba Geigy Ag	Endoplasmatisches retikulum-ständige rekombinante dibasische endoprotease und deren verwendungen

1999
- 1999-11-05 ES ES99955836T patent/ES2315022T3/es not_active Expired - Lifetime
- 1999-11-05 JP JP2000581231A patent/JP4463988B2/ja not_active Expired - Fee Related
- 1999-11-05 AU AU12629/00A patent/AU1262900A/en not_active Abandoned
- 1999-11-05 EP EP99955836A patent/EP1127154B1/fr not_active Expired - Lifetime
- 1999-11-05 WO PCT/DK1999/000607 patent/WO2000028065A1/fr not_active Ceased
- 1999-11-05 AT AT99955836T patent/ATE408020T1/de not_active IP Right Cessation
- 1999-11-05 DE DE69939548T patent/DE69939548D1/de not_active Expired - Lifetime
2000
- 2000-04-25 US US09/558,027 patent/US6329176B1/en not_active Expired - Lifetime
2001
- 2001-11-13 US US10/044,426 patent/US20020160458A1/en not_active Abandoned

Also Published As

Publication number	Publication date
ATE408020T1 (de)	2008-09-15
US6329176B1 (en)	2001-12-11
WO2000028065A1 (fr)	2000-05-18
EP1127154B1 (fr)	2008-09-10
US20020160458A1 (en)	2002-10-31
EP1127154A1 (fr)	2001-08-29
AU1262900A (en)	2000-05-29
JP4463988B2 (ja)	2010-05-19
JP2003523168A (ja)	2003-08-05
DE69939548D1 (de)	2008-10-23

Publication	Publication Date	Title
ES2315022T3 (es)	2009-03-16	Metodo para la produccion de fvii.
EP0574402B2 (fr)	2012-08-01	Expression de pace dans des cellules hotes et procedes d'utilisation
AU2005274406B2 (en)	2010-07-01	Modified vitamin K dependent polypeptides
KR101641899B1 (ko)	2016-08-01	혈액 응고 인자를 포함하는 단백질분해적으로 절단가능한 융합 단백질
KR101273229B1 (ko)	2013-06-11	변형된 활성화 특성을 갖는 응고 인자 ｘ 폴리펩타이드
CN101501216B (zh)	2013-10-02	制备重组人凝血酶的方法
DK2032607T4 (en)	2017-05-15	Proteolytic cleavable fusion protein comprising a blood coagulation factor
CZ298298B6 (cs)	2007-08-22	Analogy faktoru X s modifikovanými štepnými místyproteas, preparáty tyto látky obsahující, jejich použití a zpusob jejich výroby
EP2576625B1 (fr)	2018-04-25	Protéine de fusion ayant une activité de facteur vii
KR101492422B1 (ko)	2015-02-12	치료용 폴리펩타이드의 생체내 회수율을 증가시키는 방법
ES2503365T5 (es)	2017-10-31	Método para producir proteínas dependientes de vitamina K biológicamente activas por métodos recombinantes
CA2611708A1 (fr)	2007-01-11	Transfection stable sans serum et production de proteines humaines recombinees dans des lignees cellulaires humaines
US6958322B1 (en)	2005-10-25	Factor X analog with an improved ability to be activated
Kovnir et al.	2018	A highly productive CHO cell line secreting human blood clotting factor IX
ES2260255T3 (es)	2006-11-01	Polipeptidos furina mutados con caracteristicas mejoradas.
US8679783B2 (en)	2014-03-25	Recombinant factor X with no glycosylation and method for preparing the same
AU2020242945B2 (en)	2025-06-26	Factor IX variants and uses thereof in therapy
JP2024180602A (ja)	2024-12-26	第ｘａ因子及び誘導体を調製するための組成物及び方法
Denault et al.	2000	Comparative characterization of two forms of recombinant human SPC1 secreted from Schneider 2 cells
US9243237B2 (en)	2016-01-26	Method for mass production of factor VII/VIIA
EP1026250A1 (fr)	2000-08-09	Constructions d'ADN comprenant des facteurs de coagulation sanguine et la P-sélectine
US20160215278A1 (en)	2016-07-28	Method for mass production of factor vii/viia derivatives
AU2013202566A1 (en)	2013-05-02	Proteolytically cleavable fusion protein comprising a blood coagulation factor
AU2004276687A1 (en)	2005-04-07	Method of cleaving polypeptide by using OmpT protease mutant
KR20140101877A (ko)	2014-08-20	혈액 응고 인자를 포함하는 단백질분해적으로 절단가능한 융합 단백질